Multivariate PLS Modeling of Apicomplexan FabD-Ligand Interaction Space for Mapping Target-Specific Chemical Space and Pharmacophore Fingerprints

Biomolecular recognition underlying drug-target interactions is determined by both binding affinity and specificity. Whilst, quantification of binding efficacy is possible, determining specificity remains a challenge, as it requires affinity data for multiple targets with the same ligand dataset. Thus, understanding the interaction space by mapping the target space to model its complementary chemical space through computational techniques are desirable. In this study, active site architecture of FabD drug target in two apicomplexan parasites viz. Plasmodium falciparum (PfFabD) and Toxoplasma gondii (TgFabD) is explored, followed by consensus docking calculations and identification of fifteen best hit compounds, most of which are found to be derivatives of natural products. Subsequently, machine learning techniques were applied on molecular descriptors of six FabD homologs and sixty ligands to induce distinct multivariate partial-least square models. The biological space of FabD mapped by the various chemical entities explain their interaction space in general. It also highlights the selective variations in FabD of apicomplexan parasites with that of the host. Furthermore, chemometric models revealed the principal chemical scaffolds in PfFabD and TgFabD as pyrrolidines and imidazoles, respectively, which render target specificity and improve binding affinity in combination with other functional descriptors conducive for the design and optimization of the leads.

Investigation on the origin of exchange bias in epitaxial, oriented and polycrystalline Fe3O4 thin films

We observe exchange bias (EB) in a single magnetic film Fe3O4 at temperature T < 200 K. Irrespective of crystallographic orientations of grown Fe3O4; they exhibit similar nature of EB for (100) epitaxial, (111) oriented and polycrystalline Fe3O4 thin films. Growth induced defects such as anti-phase boundaries (APBs) in epitaxial Fe3O4 thin film is known to have an influence on the magnetic interaction. But, it is noticed that according to the common consensus of APBs alone cannot explain the origin of EB. If majority of APBs end up with mainly anti-ferromagnetic interactions across these boundaries together with the internal ordering modification in Fe3O4, then EB can emerge at low temperatures. Hence, we propose the idea of directional anti-ferromagnetic APB induced EB in Fe3O4 triggered by internal ordering for T <= 200 K. Similar arguments are extended to (111) oriented as well as polycrystalline Fe3O4 films where the grain boundaries can impart same consequence as that of APBs. (C) 2015 Author(s).

Length scales in glass-forming liquids and related systems: a review

The central problem in the study of glass-forming liquids and other glassy systems is the understanding of the complex structural relaxation and rapid growth of relaxation times seen on approaching the glass transition. A central conceptual question is whether one can identify one or more growing length scale(s) associated with this behavior. Given the diversity of molecular glass-formers and a vast body of experimental, computational and theoretical work addressing glassy behavior, a number of ideas and observations pertaining to growing length scales have been presented over the past few decades, but there is as yet no consensus view on this question. In this review, we will summarize the salient results and the state of our understanding of length scales associated with dynamical slow down. After a review of slow dynamics and the glass transition, pertinent theories of the glass transition will be summarized and a survey of ideas relating to length scales in glassy systems will be presented. A number of studies have focused on the emergence of preferred packing arrangements and discussed their role in glassy dynamics. More recently, a central object of attention has been the study of spatially correlated, heterogeneous dynamics and the associated length scale, studied in computer simulations and theoretical analysis such as inhomogeneous mode coupling theory. A number of static length scales have been proposed and studied recently, such as the mosaic length scale discussed in the random first-order transition theory and the related point-to-set correlation length. We will discuss these, elaborating on key results, along with a critical appraisal of the state of the art. Finally we will discuss length scales in driven soft matter, granular fluids and amorphous solids, and give a brief description of length scales in aging systems. Possible relations of these length scales with those in glass-forming liquids will be discussed.